Category: Stroke

HINTS vs. ABCD2 in Dizziness

Dizziness in the Emergency Department sends everyone down their favorite diagnostic algorithm, with outcomes ranging from utterly benign to impending permanent disability.  I’ve covered the repurposing of the ABCD2 score for risk-stratification in dizziness before, showing it had some utility in predicting posterior circulation stroke.

However, unsurprisingly, these authors demonstrate examination maneuvers specifically targeted at evaluating cerebellar function outperform risk-stratification.  The HINTS (head impulse, nystagmus type, test of skew) evaluation compared with the ABCD2 (age, blood pressure, clinical features, duration, diabetes) in a convenience sample of 190 prospectively collected patients with acute vestibular syndrome.  Of these 190 patients, 124 had a central cause for their vertigo (stroke, hemorrhage, space-occupying lesion).  The sensitivity and specificity of the ABCD2 score in predicting a central lesion was 58.1% and 60.6%, respectively, while the HINTS score resulted in 96.8% and 98.5%, respectively.

It’s a bit of a straw-man comparison – considering the ABCD2 score was never designed to detect posterior circulation stroke, only to affect probability estimates for cerebrovascular disease.  The prevalence of disease in this sample probably also leads to an overestimation of the specificity of the HINTS exam, but it has otherwise been found to have very good test characteristics.

Visit EMCrit for more information and video footage of the HINTS test, if you’re not already using it.

“HINTS Outperforms ABCD2 to Screen for Stroke in Acute Continuous Vertigo and Dizziness”
http://www.ncbi.nlm.nih.gov/pubmed/24127701

tPA for TIA?!

A guest post by Anand Swaminathan (@EMSwami) of EM Lyceum and Essentials of EM fame.

Over the last year, the debate over the use of alteplase in acute ischemic stroke has continued to heat up. The issue really boiled over in June after BMJ reporter Jeanne Lenzer wrote a scathing evaluation of clinical guidelines after the publication of the new ACEP Clinical Policy on the use of alteplase in ischemic stroke. Now, to muddy the waters further, enter the discussion of giving alteplase to transient ischemic attacks (TIAs).

That’s right, this week, the American Journal of Emergency Medicine published a case report discussing the administration of alteplase to a patient that the treating physicians agreed had a TIA. Before we get into the article itself, let’s take a stroll back in time to 1995.

On December 14th, 1995, the NEJM published the NINDS trial and ushered in the era of alteplase for acute ischemic stroke. One of the major exclusions in the study, and one that few have argued with, was “rapidly improving or minor symptoms.” In essence, NINDS sought to exclude patients with TIAs. The reason for this is elegantly stated by Dr. David Liebeskind (UCLA Stroke Center):

“Thrombolysis is not a rational or evidence-based therapeutic option for transient ischemia irrespective of vascular status . . . The prevailing obsession with arterial occlusion has erroneously focused attention on clots rather than ischemia . . . Imaging of occlusion without consideration of clinical details or pahtophysiolgical mechanisms may therefore be misleading.” (Stroke 2010).

From a pathophysiological and outcome standpoint, there is no good reason to administer alteplase to a patient with a TIA regardless of imaging. If the patient has an NIHSS of 0, there is no room for improvement, only harm.

In spite of this, the authors of the above case report recount the story of a 37-year-old woman who presented with a TIA. Her presenting NIHSS was 0. CT angiogram showed a “near total occlusion of the M2 segment of the MCA.” There is no report about the presence of an ischemic penumbra.  After the CTA was completed, the patients’ symptoms returned but then rapidly resolved. At this point, the physicians decided to administer alteplase in spite of the absence of symptoms. She was then transferred to a stroke center for consideration of neurointerventional care (a therapy proven not to work. See NEJM March 2013). Interestingly, the authors base their decision to treat on imaging findings but never discuss the resolution of these findings after therapy (i.e. no mention of repeat CTA or MRI/MRA).

What does this tell us about alteplase for TIA? Not much. This is a case report and gives us no information about causality of treatment. It doesn’t even show efficacy of concept because pathophysiologically the idea of giving alteplase to a TIA doesn’t make sense.  The authors talk about weighing risks and benefits outside of standard indications and contraindications. But what they have done is give a potentially dangerous, life-threatening medication to a patient with no disability at the time of administration. They have taken on all the risk of the drug without any potential benefit.

What this report really shows is the concept of “indication creep.” Earlier this year, the TREAT task force recommended that patients with rapidly resolving symptoms (but some continued deficit) should be considered for thrombolytic treatment (Stroke 2013). This recommendation wasn’t based on any literature but rather an expert consensus from a meeting sponsored by Genentech (Boehringer-Ingelheim in Europe). This case report is simply the logical extension of an illogical idea: if thrombolytics should be given to a patient with rapidly resolving symptoms, why not give it to one with no symptoms but imaging abnormalities?

The authors conclude by pointing the finger at EM physicians stating that we, “have been historically slow in adopting thrombolytic therapy for CVA.” We haven’t embraced this treatment because we don’t see definitive evidence that it works and we do see the potential harms. A month ago at ACEP, a group of EPs voted 75% to 25% to reconsider the ACEP clinical policy on tPA. The authors go on to suggest that this patient did well and required no further treatments because she received “off-label” thrombolytics. This link violates everything we know about research. Just because something happens after you do something, doesn’t mean the thing you did caused the outcome. Domhnall Brannigan told a wonderful story during his lecture at SMACC last year about a patient who presented with stroke-like symptoms and nausea. Dr. Brannigan gave the patient ondansetron for the nausea and minutes later the patient had resolution of his symptoms. None of us, though, are rushing to give ondansetron for ischemic CVA. The proposition by these authors is just as ludicrous.

“TPA for TIA: The case for “off-label” use of thrombolytics.”
http://www.ajemjournal.com/article/S0735-6757(13)00747-X/fulltext

References
Sobel RM, Wu DT, Hester K, Anda K. tPA for TIA: The case for “off-label” use of thrombolytics. Am J EM 2013; 06 November 2013 (10.1016/j.ajem.2013.10.046

The National Institute of Neurological Disorders and Stroke, rt-PA Stroke Study Group. Tissue Plasminogen Activator for Acute Ischemic Stroke. NEJM 1995; 333(24): 1581-7.

Liebskind DS. No-Go to tPA for TIA. Stroke 2010; 41(12): 3005-6.

The Re-examining Acute Eligibility for Thrombolysis (TREAT) Task Force. Levine SR, Khatri P, Broderick JP, Grotta JC et al. Review, historical context, and clarifications fo the NINDS rt-PA stroke trials exclusion criteria: part 1: rapidly improving stroke symptoms. Stroke 2013; 44: 2500-2505

tPA for TIA?!

A guest post by Anand Swaminathan (@EMSwami) of EM Lyceum and Essentials of EM fame.

Over the last year, the debate over the use of alteplase in acute ischemic stroke has continued to heat up. The issue really boiled over in June after BMJ reporter Jeanne Lenzer wrote a scathing evaluation of clinical guidelines after the publication of the new ACEP Clinical Policy on the use of alteplase in ischemic stroke. Now, to muddy the waters further, enter the discussion of giving alteplase to transient ischemic attacks (TIAs).

That’s right, this week, the American Journal of Emergency Medicine published a case report discussing the administration of alteplase to a patient that the treating physicians agreed had a TIA. Before we get into the article itself, let’s take a stroll back in time to 1995.

On December 14th, 1995, the NEJM published the NINDS trial and ushered in the era of alteplase for acute ischemic stroke. One of the major exclusions in the study, and one that few have argued with, was “rapidly improving or minor symptoms.” In essence, NINDS sought to exclude patients with TIAs. The reason for this is elegantly stated by Dr. David Liebeskind (UCLA Stroke Center):

“Thrombolysis is not a rational or evidence-based therapeutic option for transient ischemia irrespective of vascular status . . . The prevailing obsession with arterial occlusion has erroneously focused attention on clots rather than ischemia . . . Imaging of occlusion without consideration of clinical details or pahtophysiolgical mechanisms may therefore be misleading.” (Stroke 2010).

From a pathophysiological and outcome standpoint, there is no good reason to administer alteplase to a patient with a TIA regardless of imaging. If the patient has an NIHSS of 0, there is no room for improvement, only harm.

In spite of this, the authors of the above case report recount the story of a 37-year-old woman who presented with a TIA. Her presenting NIHSS was 0. CT angiogram showed a “near total occlusion of the M2 segment of the MCA.” There is no report about the presence of an ischemic penumbra.  After the CTA was completed, the patients’ symptoms returned but then rapidly resolved. At this point, the physicians decided to administer alteplase in spite of the absence of symptoms. She was then transferred to a stroke center for consideration of neurointerventional care (a therapy proven not to work. See NEJM March 2013). Interestingly, the authors base their decision to treat on imaging findings but never discuss the resolution of these findings after therapy (i.e. no mention of repeat CTA or MRI/MRA).

What does this tell us about alteplase for TIA? Not much. This is a case report and gives us no information about causality of treatment. It doesn’t even show efficacy of concept because pathophysiologically the idea of giving alteplase to a TIA doesn’t make sense.  The authors talk about weighing risks and benefits outside of standard indications and contraindications. But what they have done is give a potentially dangerous, life-threatening medication to a patient with no disability at the time of administration. They have taken on all the risk of the drug without any potential benefit.

What this report really shows is the concept of “indication creep.” Earlier this year, the TREAT task force recommended that patients with rapidly resolving symptoms (but some continued deficit) should be considered for thrombolytic treatment (Stroke 2013). This recommendation wasn’t based on any literature but rather an expert consensus from a meeting sponsored by Genentech (Boehringer-Ingelheim in Europe). This case report is simply the logical extension of an illogical idea: if thrombolytics should be given to a patient with rapidly resolving symptoms, why not give it to one with no symptoms but imaging abnormalities?

The authors conclude by pointing the finger at EM physicians stating that we, “have been historically slow in adopting thrombolytic therapy for CVA.” We haven’t embraced this treatment because we don’t see definitive evidence that it works and we do see the potential harms. A month ago at ACEP, a group of EPs voted 75% to 25% to reconsider the ACEP clinical policy on tPA. The authors go on to suggest that this patient did well and required no further treatments because she received “off-label” thrombolytics. This link violates everything we know about research. Just because something happens after you do something, doesn’t mean the thing you did caused the outcome. Domhnall Brannigan told a wonderful story during his lecture at SMACC last year about a patient who presented with stroke-like symptoms and nausea. Dr. Brannigan gave the patient ondansetron for the nausea and minutes later the patient had resolution of his symptoms. None of us, though, are rushing to give ondansetron for ischemic CVA. The proposition by these authors is just as ludicrous.

“TPA for TIA: The case for “off-label” use of thrombolytics.”
http://www.ajemjournal.com/article/S0735-6757(13)00747-X/fulltext

References
Sobel RM, Wu DT, Hester K, Anda K. tPA for TIA: The case for “off-label” use of thrombolytics. Am J EM 2013; 06 November 2013 (10.1016/j.ajem.2013.10.046

The National Institute of Neurological Disorders and Stroke, rt-PA Stroke Study Group. Tissue Plasminogen Activator for Acute Ischemic Stroke. NEJM 1995; 333(24): 1581-7.

Liebskind DS. No-Go to tPA for TIA. Stroke 2010; 41(12): 3005-6.

The Re-examining Acute Eligibility for Thrombolysis (TREAT) Task Force. Levine SR, Khatri P, Broderick JP, Grotta JC et al. Review, historical context, and clarifications fo the NINDS rt-PA stroke trials exclusion criteria: part 1: rapidly improving stroke symptoms. Stroke 2013; 44: 2500-2505

Letter in JAMA

A couple months back, JAMA published Jeff Saver’s time-to-tPA association, derived from the Get With the Guidelines-Stroke Registry.  My critique of this article remains essentially the same, but this past issue JAMA published an edited version as a response to Dr. Saver.

While many of you will find the content behind the JAMA paywall, the basic gist of Saver’s response to my letter is:

  • tPA-treated stroke mimics are not included in the GWTG-Stroke registry during the study period.  It is an optional reporting field.
  • The tiny bit of data from original NINDS showed rapidly-improving patients from the placebo group were equally distributed between 59 to 90 minutes and 91 to 180 minutes (3/145 vs. 4/167).
  • The onset-to-treatment-time and outcome association was consistent between NIHSS 0-14 and NIHSS 15-42, and therefore any effects from TIAs must be insignificant.

In summary: they don’t really know how many TIAs/stroke mimics/aborted strokes there were, but they can draw lines around some numbers to support their conclusion.

These are reasonable responses from their standpoint.  I would point out, however, the NINDS group made specific efforts to exclude “rapidly improving” symptoms from inclusion, probably resulting in extreme extra care in preventing enrollment of TIAs.  This population is unlikely to be generalizable to current tPA-happy practice across medicine.  They do not, unfortunately, address the problem of “aborted stroke” coding, which further received a shout-out on Twitter from Dr. Hsia:

@emlitofnote hit the mark in @JAMA_current with citing our averted #stroke paper: #tPA-treated does not equal #stroke http://t.co/6aE7bFlm7k
— Amie Hsia (@DCStrokeDoc) November 8, 2013

I’ll try and get a peek at the GWTG-Stroke data myself, but with the literature documenting anywhere from 2% to 31% stroke mimic treatment rate – with the actual true rate probably exactly in the middle of that range – it’s critically important to uncover risks and costs of inappropriate tPA administration.  If the GWTG-Stroke registry is a true quality device, it needs to do a better job of measuring adverse events.

Or, you could end up like Houston Texans’ coach Gary Kubiak, who received tPA last week for a stroke mimic (currently reported as having had a TIA – which I find dubious, but I have no personal knowledge of the case).

“Acute Ischemic Stroke and Timing of Treatment”
http://www.ncbi.nlm.nih.gov/pubmed/24193085

Intracranial Angioplasty, Where Did We Go Wrong?

This week The Lancet published a friendly reminder from the SAMMPRIS investigators warning us that it is a bad idea to go putting stents in places they do not belong. This unintended favor came in the form of the publication of the long term follow-up from the Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis trial online this week in The Lancet.

The SAMMPRIS trial, originally published in the NEJM in 2011 applied the frequently  attempted, but rarely accurate mantra,“If it works on the heart then it should work on the brain.” The authors took high risk TIA patients with radiologically confirmed intracranial stenosis and randomized them to “aggressive” medical management or percutaneous transluminal angioplasty and stenting (PTAS). The trial was stopped early because of the exorbitant amount of periprocedural strokes and death among those in the PTAS group. Specifically there was an 8.9% absolute increase in stroke and 1.8% increase in mortality within the first 30 days of enrollment. The authors’ summary of this dramatic failure was that the true benefits and harms could not be assessed at the time of initial publication, as there was not enough data to determine if the long term benefits outweighed these initial harms.

The recent paper is the 2-year follow up of this cohort and specifically addresses these presumed “long term benefits”. The overall occurrence of stroke was 19% in the medically managed group vs 26% in the PTAS group. It is apparent no clinically significant benefit exists especially when considering the devastating early harms. Yet another example of our limited understanding of the pathophysiology of atherosclerotic disease, and the ramifications of introducing thrombogenic objects into already tight spaces.

“Aggressive Medical Treatment With or Without Stenting in High-Risk Patients with Intracranial Artery Stenosis (SAMMPRIS): the Final Results of a Randomized Trial” http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)62038-3/fulltext

Nihilism, Emergency Medicine, and the art of doing nothing at emnerd.com and @CaptainBasilEM

Intracranial Angioplasty, Where Did We Go Wrong?

This week The Lancet published a friendly reminder from the SAMMPRIS investigators warning us that it is a bad idea to go putting stents in places they do not belong. This unintended favor came in the form of the publication of the long term follow-up from the Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis trial online this week in The Lancet.

The SAMMPRIS trial, originally published in the NEJM in 2011 applied the frequently  attempted, but rarely accurate mantra,“If it works on the heart then it should work on the brain.” The authors took high risk TIA patients with radiologically confirmed intracranial stenosis and randomized them to “aggressive” medical management or percutaneous transluminal angioplasty and stenting (PTAS). The trial was stopped early because of the exorbitant amount of periprocedural strokes and death among those in the PTAS group. Specifically there was an 8.9% absolute increase in stroke and 1.8% increase in mortality within the first 30 days of enrollment. The authors’ summary of this dramatic failure was that the true benefits and harms could not be assessed at the time of initial publication, as there was not enough data to determine if the long term benefits outweighed these initial harms.

The recent paper is the 2-year follow up of this cohort and specifically addresses these presumed “long term benefits”. The overall occurrence of stroke was 19% in the medically managed group vs 26% in the PTAS group. It is apparent no clinically significant benefit exists especially when considering the devastating early harms. Yet another example of our limited understanding of the pathophysiology of atherosclerotic disease, and the ramifications of introducing thrombogenic objects into already tight spaces.

“Aggressive Medical Treatment With or Without Stenting in High-Risk Patients with Intracranial Artery Stenosis (SAMMPRIS): the Final Results of a Randomized Trial” http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)62038-3/fulltext

Nihilism, Emergency Medicine, and the art of doing nothing at emnerd.com and @CaptainBasilEM

Ischemic Stroke – Shaken, Not Stirred

It’s always mildly entertaining when stroke neurologists flip hats – from espousing the success of tPA to promoting the Next Big Thing.  This is when you hear tPA’s greatest proponents admitting “only 20% to 30% of patients have complete recanalization within 2 hours of intravenous tPA” or “one third of those with any recanalization experience reocclusion.”

Ah, sigh.

But, regardless, this study is about the Next Big Thing – which is a transcranial sonothrombolysis helmet.  This safety evaluation of 20 patients starts with IV tPA as indicated, and then continues with this operator-independent 2-MHz pulsed-wave ultrasound through a special headband.  The theory, of course, is there will be gaseous microbubbles at the site of occlusion that increase efficacy of tPA and further prevent reocclusion.  This safety study had a primary endpoint of 10% symptomatic intracranial hemorrhage with a power of 0.80.

Good news!  There were no episodes of sICH.  But, however, 6 out of 20 (30%) had asymptomatic ICH.  And, then, in the ultimate safety outcome – there were 4 deaths resulting from the 14 other serious adverse events.  These deaths were mostly progression of cerebral edema and related consequences, and the authors state they were unrelated to the study device.

The first author is on the scientific advisory board for the device manufacturer – which is not disclosed in the text.  The second author holds the patent for the device and is Chair of their scientific advisory board.  The Texas Board of Regents is the asignee for the patent for the device, and is one of two sponsoring institutions.  And, as the authors note, “other limitations include possible selection bias and investigators unblinded to treatment.”

The median NIHSS was 15, so some poor outcomes are to be expected – but, still, I think this is only convincingly safe if you have financial conflicts of interest.

“CLOTBUST-Hands Free – Pilot Safety Study of a Novel Operator-Independent Ultrasound Device in Patients With Acute Ischemic Stroke”
http://www.ncbi.nlm.nih.gov/pubmed/24159060

ACEP/AAN Guideline Writers Respond

Some of the authors of the new ACEP/AAN clinical policy have responded to the BMJ report discussing conflict-of-interest in guidelines, focusing on the science behind the tPA portion.

If you haven’t already visited, it’s truly a star-studded sort of discussion, with David Newman, Jerome Hoffman, Robert Solomon, Jeffrey Saver, Stephen Messe, Peter Sandercock, and James Grotta, among others.

Letter in Stroke

My correspondence regarding this article was published in Stroke a couple days ago.  I’d like to say the author response is earth-shattering and insightful, but while it is not, they were kind enough to respectfully reply.

Sadly, the correspondence and response is available only to subscribers – but I have PDFs available for educational purposes….

“Letter by Radecki Regarding Article, ‘Safety of Thrombolysis in Stroke Mimics: Results From a Multicenter Cohort Study'”http://stroke.ahajournals.org/content/early/2013/08/08/STROKEAHA.113.002040.full.pdf+html

tPA Proponents Want to Have It Both Ways

I’m sure I sound like a bit of a broken record – yet again covering further attempts by the stroke neurology literature to continue expanding use of tPA for acute stroke beyond its initial, narrowly selected treatment population.  This observational, retrospective review from SITS-ISTR would like you to know:

“…this is the first observational study demonstrating that intravenous alteplase therapy within 4.5 to 6 hours of stroke onset for patients compliant with other EU approval criteria resulted in comparable rates of SICH, mortality, and functional independence to treatment initiated within 3 hours. This observation persisted in the multivariate analysis after adjustment for baseline imbalances.”

No difference in outcomes between 0-3h, 3-4.5h, and 4.5-6h – in both guideline-compliant and protocol-violation cohorts, and both adjusted and unadjusted results.  The authors, all receiving honoraria or grant support from Boehringer Ingelheim would like you to believe this analysis, also funded by Boehringer Ingelheim, supports a benefit for tPA up to six hours.

…but didn’t we just cover Jeff Saver’s JAMA article that “proved” an obvious time-to-treatment effect, favoring faster treatment?

Which of these observational, retrospective, registry reviews provides us the truth?  Is there a time-to-treatment effect that decays benefit with time, or, as this registry suggests, no difference between any time frames?

I suppose it depends on your specific professional conflicts-of-interest.

“Results of Intravenous Thrombolysis Within 4.5 to 6 Hours and Updated Results Within 3 to 4.5 Hours of Onset of Acute Ischemic Stroke Recorded in the Safe Implementation of Treatment in Stroke International Stroke Thrombolysis Register (SITS-ISTR)”
www.ncbi.nlm.nih.gov/pubmed/23689267‎